fever without source in children 0 to 36 months of age · fever, one of the most common chief...

Pediatr Clin N Am 53 (2006) 167–194

Fever Without Source in Children

0 to 36 Months of Age

Paul Ishimine, MD

Department of Emergency Medicine, University of California, San Diego Medical Center,

200 West Arbor Drive, San Diego, CA 92103-8676, USA

Fever, one of the most common chief complaints of children seeking medical

attention [1,2], prompted over 5 million emergency department (ED) visits in

2002 [3]. Most of these children have identifiable causes of their fevers, but many

will have fever without an apparent source (FWS) after conclusion of the history

and physical examination. Despite the frequency of fever as a chief complaint,

there is considerable controversy in the management of the young child who

has FWS [4–8]. The challenge in the evaluation of the febrile young child lies

in balancing the minimization of risk to the patient with the costs of testing

and treatment.

Definition of fever

A variety of temperatures have been used to define fever, but the most

commonly accepted definition of fever is a temperature of �38.08C (100.48F), avalue derived from studies by Wunderlich, who took 1 million measurements on

25,000 patients and determined that this temperature was the upper limit of

normal [9]. Although less invasive means of measuring temperature exist, such as

axillary and aural thermometry, the variability of measurements at these sites

[10–12] warrants using the current outpatient reference standard, rectal ther-

mometry, when measuring temperatures in young children. An accurate tempera-

ture measurement is especially important if a practitioner chooses to use fever

guidelines because the implementation of these guidelines is initiated once a

patient meets a certain temperature threshold.

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ishimine168

Once it is determined that a child has a fever, measured in the emergency

department or in the practitioner’s office, further evaluation can then proceed.

However, a child who presents with a reported fever at home but who is afebrile

in the ED or in the office poses more of a challenge. Parents may not be able to

accurately define fever [13], and subjective assessment by parents has been

shown to have generally good but variable sensitivity in the detection of fever

[14–16]. Parental assessment is often colored by ‘‘fever phobia,’’ inaccurate

concerns and misconceptions about the potential danger of fever [17,18].

Additionally, bundling of infant creates confusion for both providers and parents

because bundling of infants may raise the skin temperature but not rectal tem-

perature [19]. However, a fever measured at home with rectal thermometry gen-

erally warrants the same concern as a fever measured in the ED or in the office.

Six of 63 patients with bacteremia or bacterial meningitis in a large office-based

study of young febrile infants were found to be afebrile in physicians’ offices but

were febrile at home [20].

Epidemiology

The management of the febrile young child continues to evolve. Contributing

to this confusion is the changing epidemiology of bacterial infection in young

children. Haemophilus influenzae previously presented a significant burden of

disease, resulting in substantial morbidity and mortality in young children.

H influenzae represented 19% of all positive cultures in febrile children who

presented to a pediatric walk-in clinic in 1972 [21], but after widespread use of

the H influenzae type b vaccine starting in 1991, the epidemiology of invasive

bacterial disease changed dramatically. H influenzae type b has been nearly

eliminated [22,23], with a 94% decline in H influenzae meningitis shortly after

the introduction of the Hib vaccine [24]. Combining the results of two large

studies of occult bacteremia in patients seen in the mid 1990s in Boston and

Philadelphia, there were no blood cultures that grew H influenzae from 15,366

patients seen in these pediatric emergency departments [25,26].

Corresponding to the decrease in invasive disease caused by H influenzae,

there has been an increase in the percentage of invasive diseases caused by

Streptococcus pneumoniae. The burden of disease caused by S pneumoniae has

been significant. S pneumoniae represented 83% to 92% of positive blood

cultures taken from young febrile children presenting to EDs in the mid 1990s,

and the overall prevalence of occult bacteremia was 1.6% to 1.9% [25,26]. In

1998, there were an estimated 12,560 cases of invasive pneumococcal disease

(bacteremia, meningitis, and pneumonia) and 110 deaths in children younger than

2 years of age, with a case fatality rate of 1.4% [27]. This low overall case fatality

rate likely reflects the generally good outcomes in patients with bacteremia,

which represented 75% of the invasive disease in this population [27]. However,

the case fatality rate resulting from S pneumoniae meningitis is higher than

fever without source in children 0–36 months of age 169

meningitis caused by Neisseria meningitidis, Streptococcus group B, Listeria

monocytogenes, or H influenzae [24]. Additionally, there has been an increas-

ing prevalence of multidrug resistant S pneumoniae, and the proportion of

isolates with multidrug resistance is highest in children under 5 years of age

[28,29]. Although an effective, 23-valent polysaccharide pneumococcal vaccine

has been licensed since 1983, this vaccine is insufficiently immunogenic in

young children and is, therefore, ineffective and not recommended for children

younger than 2 years of age, which is the age group most at risk for invasive

pneumococcal infection.

The introduction of the heptavalent pneumococcal conjugate vaccine (PCV7),

covering the seven most common pneumococcal serotypes, has changed the land-

scape of invasive bacterial disease in young children. There are over 90 pneumo-

coccal serotypes that have been identified, but the seven serotypes included in

the vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F) cause approximately 82% of the

cases of invasive pneumococcal disease [27]. This vaccine, licensed in 2000, is

recommended for universal administration to children younger than 2 years old in

a 4-dose regimen (doses are given at 2, 4, 6, and 12–15 months), as well as to

high-risk older children (eg, children with sickle cell disease, chronic cardiac and

pulmonary diseases, and other immunocompromising conditions) [30].

This vaccine has been shown to be both safe [31] and highly effective in

preventing invasive pneumococcal disease, with a prelicensure study demon-

strating an efficacy of 97% [32]. In a postlicensure surveillance of the Northern

California Kaiser Permanente [32] study cohort, the cohort that served as the

largest prelicensure study group of the PCV7 vaccine, the incidence of invasive

pneumococcal disease caused by vaccine and cross-reactive vaccine serotypes

declined from 51.5 to 98.2 cases of invasive disease per 100,000 person-years in

children less than 1 year old to 0 cases per 100,000 person-years 4 years after

licensure [33]. There was also a reduction of invasive pneumococcal disease in

children less than 2 years old, declining from 81.7 to 113.8 cases of invasive

disease per 100,000 person-years to 0 cases per 100,000 person-years 4 years

after the vaccine was licensed [33]. There was a decline in invasive pneumo-

coccal disease for all serotypes, not just the seven covered by PCV7, with a

decline of 94% and 91% in children less than 1 year of age and 2 years of age,

respectively. There was also a significant decline in drug-resistant pneumo-

cocci and a 25% decrease in invasive pneumococcal disease in people older than

5 years old, suggesting herd immunity because these patients were not them-

selves immunized. These declines occurred despite the fact that only 24% of

children less than 2 years old received all four recommended doses because of

a vaccine shortage [33].

These findings have been replicated in other settings. In Massachusetts, there

was a 69% decline in the incidence of total invasive pneumococcal disease as

well as an 88% decline in non-meningitis vaccine-serotype disease [34]. Simi-

larly, there was a 69% decline in the total incidence of invasive pneumococcal

disease and a 78% decline in the incidence of disease caused by vaccine sero-

types, seen in a national network of regional surveillance centers administered

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by the Centers for Disease Control and Prevention, accompanied by a decline

in penicillin-resistant pneumococcal isolates [35]. There was a 66% decline in

the incidence of invasive pneumococcal infections (77% decline in vaccine-

covered serotypes) noted from a network study of children’s hospitals [36]. Three

likely mechanisms are involved in the PCV7-associated decrease in disease:

individual risk decline, decline in antibiotic-resistant bacteria, and herd immunity.

Caveats

Although the differential diagnosis of fever is quite broad and includes both

infectious and noninfectious causes [37], the majority of febrile children have

underlying infectious causes of fever. For the purposes of this article, patients

are presumed to be febrile from infectious sources. Additionally, diagnostic

strategies emphasize the detection of bacterial disease because bacterial diseases

are more likely to be associated with worse outcomes, but viral infections can

also be associated with significant morbidity and mortality, especially in youn-

ger children.

Most large studies addressing serious bacterial illness use children from large,

urban, tertiary care children’s hospital emergency departments. Physicians in

primary care settings are less compliant with ED-derived recommendations for

the evaluation and treatment of febrile children, but compared with ED patients,

outcomes for these patients are similar [20,38]. This similarity in outcome may

be the result of several causes: the sickest patients may preferentially present to

the ED, patients may get closer follow-up by their primary care providers, the

judgment of primary care providers may be more sensitive than criteria put forth

in various guidelines, or because the likelihood of serious disease in these chil-

dren is low [39].

Finally, most studies of febrile young children exclude patients who have

potentially complicating risk factors. These studies typically have excluded chil-

dren who are immunocompromised (eg, sickle cell disease, cancer, or long-term

steroid use), have indwelling medical devices (eg, ventriculoperitoneal shunts and

indwelling venous access catheters), are currently taking antibiotics, or have

prolonged fevers (� 5 days).

Approach to the young febrile child

History and physical examination

The history and physical examination are invaluable in the assessment of the

febrile child. The level and duration of a child’s fever as well as the mode of

temperature measurement are important to note. There is an increase in the

prevalence of pneumococcal bacteremia with an increase in temperature [40], and

this is more pronounced in young children. In children less than 3 months of age


who have temperatures � 40.08C, 38% have serious bacterial infection [41]. The

duration of the fever itself at the time of ED presentation does not predict whether

a child has occult bacteremia [42]. The use of antipyretics should be noted.

Parents often give inaccurate doses of antipyretics [43,44], and paradoxically, in

one study, patients treated with antipyretics presented to the ED with higher

temperatures than those patients who were untreated at home [45]. A response

(or lack thereof) to antipyretic medications does not predict whether the un-

derlying cause is bacterial or viral [45–49]. Additional important data include

associated signs and symptoms, underlying medical conditions, exposure to ill

contacts, and immunization status.

An assessment of the child’s overall appearance is critical. If a child appears to

be toxic, this mandates an aggressive work-up, antibiotic treatment, and hos-

pitalization, regardless of age or risk factors. The physical examination may re-

veal obvious sources of infection, and the identification of a focal infection may

decrease the need for additional testing. For example, febrile patients with

recognizable viral conditions (eg, croup, chickenpox, and stomatitis) have lower

rates of bacteremia than patients with no obvious source of infection [50]. Simi-

larly, febrile children with influenzavirus A have lower rates of serious bacterial

infections compared with febrile children without influenzavirus A [51]. Febrile

patients with otitis media appear to have the same rate of bacteremia as febrile

children without otitis media [52,53].

With the exception of neonates and young infants, if a child has a nontoxic

appearance, a more selective approach can be undertaken. When a child who has

a febrile illness has an obviously identifiable cause, the treatment and disposition

should generally be tailored to this specific infection. The approach to the young

child who has FWS is discussed below.

Age-specific considerations

The approach to the young child who has a fever without a source varies

depending on the age of the child. Traditionally, young children have been cate-

gorized in into three distinct age groups for the purposes of fever evaluation:

the neonate (0–28 days old), the young infant (commonly defined as infants

between 1 and 3 months of age, although some authors define this group to in-

clude children only between 1 and 2 months of age), and the older infant or

toddler (commonly defined as 3 to 36 months of age, although some studies

include patients only up to 24 months old in this group). Although the use of

chronologic age distinctions are somewhat artificial (for example, the difference

in the risk of serious bacterial illness is likely to be inconsequentially different

between a 28-day-old child and a 29-day-old child), there is some rationale

behind these seemingly arbitrary age distinctions. Younger children have de-

creased immunologic function and are more commonly infected with virulent or-

ganisms. Additionally, the physical examination is more difficult because young

children have a limited behavioral repertoire.

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Young infants: 0 to 3 months old

The traditional approach to young infants has included aggressive inves-

tigation, antibiotic administration, and hospital admission [54]. However, the

hospitalization of young infants can result in iatrogenic complications, financial

ramifications, and parental stress [55,56]. Recently, this approach has been chal-

lenged, and the current recommendations are not as strict regarding mandatory

admission in well-appearing infants over 28 days old.

Neonates: birth to 28 days old

Neonates are at a particularly high risk for SBI. The majority of febrile

neonates presenting to the ED are diagnosed ultimately as having a nonspe-

cific viral illness, but approximately 12% of all febrile neonates presenting to

a pediatric emergency department have serious bacterial illness [57,58]. When

they are infected, neonates are infected typically by more virulent bacteria

(eg, Streptococci group B, Escherichia coli, and L monocytogenes) and are more

likely to develop serious sequelae from viral infections (eg, herpes simplex virus

meningitis). Streptococci group B, a common bacteria pathogen in this age

group, is associated with high rates of meningitis (39%), non-meningeal foci of

infection (10%), and sepsis (7%) [59]. This age group is the least likely to be

affected by the use of the pneumococcal vaccine because only a small percentage

of neonates are infected by this pathogen. Although infection is uncommon, those

neonates who are infected with S pneumonia have a mortality rate of 14% [60].

The most common bacterial infections in this are group are urinary tract in-

fections (UTIs) and occult bacteremia [57,58].

Evaluation of the febrile neonate

Traditional risk-stratification strategies have used ancillary testing to supple-

ment the limited information available from the history and physical exami-

nation. Unfortunately, it is difficult to predict accurately which neonates have

invasive disease, even when laboratory testing is used. Initial studies by Dagan

and colleagues [61,62] appeared promising. These ‘‘Rochester criteria’’

(Rochester, Boston, and Philadelphia criteria are discussed below) were applied

to infants less than 90 days old, and neonates were included. Using the Rochester

criteria, Jaskiewicz and colleagues [63] found that 2 of 227 children younger than

30 days old who met low-risk criteria had SBI. However, Ferrera and colleagues

[64] found that 6% of neonates who were retrospectively classified as low risk by

the Rochester criteria had SBI.

Baker and colleagues [65] retrospectively stratified neonates into high- and

low-risk patients based on the ‘‘Philadelphia criteria’’ they had derived for older

infants. The neonates who were placed in the high-risk category had a higher

incidence of bacterial disease (18.6%), but 4.6% of neonates who were classified

as low-risk patients had a serious bacterial infection. Additionally, 11 different


bacterial pathogens were identified in 32 patients with SBI, and only one of these

32 patients was infected with S pneumoniae. Kadish and colleagues [58] found a

similar rate of SBI in neonates whom they categorized as low risk when they

retrospectively applied both the Philadelphia criteria and similar criteria created

by Baskin and colleagues (the ‘‘Boston criteria’’). They also found a wide range

of bacterial pathogens, but only two cultures in 55 patients with SBI were

positive from S pneumoniae.

Because of the inability to accurately predict serious infections in this age

group, the recommendations for these patients include obtaining blood cul-

tures, urine for rapid urine testing, urine cultures, and cerebrospinal fluid (CSF)

[66,67]. A peripheral white blood cell (WBC) count is often ordered in the

evaluation of febrile neonates, but the discriminatory value of the WBC count is

insufficient to differentiate between patients with SBI versus nonbacterial

infection [68–70]. Because of the inability of the white blood cell count to

predict SBI, blood cultures should be ordered on all patients. Although various

options for rapidly testing for urinary tract infection exist (eg, urine dipstick,

standard urinalysis, and enhanced urinalysis), no rapid test detects all cases of

UTI, so urine cultures must be ordered in all of these patients [71,72]. Urine

should be collected by bladder catheterization or suprapubic aspiration because

bag urine specimens are associated with unacceptably high rates of contamination

[73,74]. A lumbar puncture should be performed in all febrile neonates. Chest

radiographs are indicated only in the presence of respiratory symptoms, and stool

analyses are indicated only in the presence of diarrhea. In neonates, the presence

of signs suggestive of viral illness does not negate the need for a full diagnostic

evaluation. Unlike older children, in whom documented respiratory syncytial

virus (RSV) infections decrease the likelihood of serious bacterial illness, RSV-

infected neonates have the same rate of SBI compared with RSV-negative

neonates [75].

Treatment and disposition of the febrile neonate

Because of the high rates of serious bacterial infections, all febrile neonates

should receive antibiotics. Typically, these patients are treated with a third-

generation cephalosporin or gentamicin. Ceftriaxone is not recommended for

neonates who have jaundice because of the concern for inducing unconjugated

hyperbilirubinemia [76–78]. Other third-generation cephalosporins, such as cefo-

taxime, 50 mg/kg intravenously (IV) (100 mg/kg if there is a concern for

meningitis based on CSF results), or gentamicin, 2.5 mg/kg IV, are used in this

age group. Additionally, although the incidence of L monocytogenes is quite low

[79], ampicillin, 50 mg/kg IV (100 mg/kg IV if there is a concern for meningitis)

is still recommended in the empiric treatment of these patients [80].

Neonatal herpes simplex virus (HSV) infections occur in approximately 1 per

3200 deliveries in the United States [81]. Neonates with HSV infections usually

present within the first 2 weeks of life, and only a minority of infected children

have fever [82]. Rates of morbidity and mortality are high with neonatal HSV, but

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treatment with high-dose acyclovir improves outcomes in patients [83]. Acy-

clovir is not recommended routinely for empiric treatment in addition to standard

antibiotics in febrile neonates [82] but should be considered in febrile neonates

with risk factors for neonatal HSV (20 mg/kg IV). Risk factors include primary

maternal infection, especially those neonates delivered vaginally, prolonged

rupture of membranes at delivery, the use of fetal scalp electrodes, skin, eye or

mouth lesions, seizures, and CSF pleocytosis [81,84,85].

Febrile neonates should be hospitalized, regardless of the results of laboratory

studies. Outpatient management of these patients has been suggested [86] and

occurs frequently when patients present to pediatricians’ offices [20]. However,

given the lack of prospective studies addressing this approach as well as the

limitations inherent in the screening evaluation in the emergency department and

frequent difficulties in arranging follow-up evaluation, hospitalization is strongly

recommended [66,67].

Young infants: 1 to 3 months old

The approach to febrile young infants, defined most commonly as children

less than either 2 or 3 months old (in this discussion, age less than 3 months will

be used), changed dramatically in the 1980s and early 1990s. Before this time,

most febrile young infants presenting to academic medical centers were hos-

pitalized and frequently started on antibiotic therapy. The aggressive approach

was based in part on the relatively limited amount of information obtainable from

examination of young infants [65,87], the high morbidity rate observed with

H influenzae type b infection, and the efficacy of antibiotics in the treatment of

serious bacterial infection.

The ‘‘Rochester criteria’’ put forth by Dagan and colleagues [61,62] stratified

children less than 60 days old into high- and low-risk groups. The children who

met these criteria appeared well, had been previously healthy, and had no evi-

dence of skin, soft tissue, bone, joint, or ear infection. Additionally, the children

had normal peripheral WBC count (5000–15,000/mm3), normal absolute band

counts (� 1500/mm3), � 10 WBC/high-power field (hpf) of centrifuged urine

sediment, and for those patients with diarrhea, � 5 WBC/hpf on stool smear

[61,62]. The low-risk group identified children who were unlikely to have serious

bacterial infection, with a negative predictive value of 98.9% [63].

In 1992, Baskin and colleagues [88] described the ‘‘Boston criteria’’ for febrile

children between 1 and 3 months of age who presented to the emergency de-

partment with temperatures � 38.08C. Infants were discharged after an intra-

muscular (IM) injection ceftriaxone, 50 mg/kg, if they generally appeared to

be well (not strictly defined) and had no ear, soft tissue, joint, or bone infec-

tions on physical examination. Furthermore, these patients had to have CSF

with � 10 WBC/hpf, microscopic UA with � 10 WBC/hpf or urine dipstick

negative for leukocyte esterase, a peripheral WBC count of � 20,000/mm3, and

normal findings in patients in whom a chest radiograph was obtained (all tests

except the chest radiograph were performed on all patients). Twenty-seven of


503 children (5.4%) were later found to have serious bacterial infection (bacterial

gastroenteritis, urinary tract infection, and occult bacteremia). Only one of nine

patients with occult bacteremia in this study were infected S pneumoniae [88].

Baker and colleagues [65] similarly sought to identify low-risk patients

between 29 and 56 days old with temperatures of � 38.28C. Patients who ap-

peared to be well (as defined by an Infant Observation Score of 10 or less), had a

peripheral WBC count of � 15,000/mm3, a band-to-neutrophil ratio of � 0.2, a

urinalysis (UA) with fewer than 10 WBC/hpf, few or no bacteria on a centrifuged

urine specimen, CSF with fewer than 8 WBC/mm3, a gram-negative stain,

negative results on chest radiographs (obtained on all patients), and stool negative

for blood and few or no WBCs on microscopy (ordered on those patients with

watery diarrhea) were considered to have a negative screen and were not treated

with antibiotics. Of the 747 consecutively enrolled patients, 65 (8.7%) had SBI.

All 65 patients who had serious bacterial infection were identified using these

screening criteria. These 65 patients had a total of 70 bacterial infection sites

where a bacterial pathogen was identified, and four of these 70 infections were

caused by S pneumoniae [65]. In a follow-up study (in which fever was defined

as � 38.08C rectally) of 422 consecutively enrolled febrile young infants,

43 (10%) had SBI, and all 101 patients who were identified as low risk had

no SBI. All 43 patients who had SBI were identified prospectively as high risk

using the Philadelphia criteria [89].

In the large studies by Baskin and Baker and colleagues, only a minority of

patients with SBI had pneumococcal infection, and thus, children in this age

group are unlikely to benefit directly from the PCV7 vaccine [65,88].

Evaluation of the febrile young infant

The clinical evaluation alone will result in a substantial number of missed SBI,

so laboratory testing is required in this age group. The white blood cell count with

differential, catheterized urinalysis, and blood and urine cultures should be

obtained in all patients. Stool studies for white blood cell counts and stool cul-

tures should be ordered in patients with diarrhea. Chest radiographs should be

obtained only in young febrile infants with signs of pulmonary disease (tachypnea

� 50 breaths/minute, rales, rhonchi, retractions, wheezing, coryza, grunting, nasal

flaring, or cough) [90,91].

Controversies in this age group surround the need for lumbar puncture.

Although the Boston and Philadelphia criteria require CSF analysis, the Roch-

ester criteria do not mandate lumbar puncture. The rarity of bacterial meningitis

contributes to the controversy surrounding the utility of the lumbar puncture.

However, the prevalence of bacterial meningitis in febrile infants less than

3 months old is 4.1 per 1000 patients, and neither the clinical examination nor the

peripheral white blood cell count is reliable in diagnosing meningitis in this age

group [68,92]; therefore, the LP should be strongly considered. Additional

controversy surrounds the need for antibiotics in patients who are identified as

low risk. Patients identified as low risk by the Philadelphia protocol were not given

ishimine176

antibiotics, whereas patients enrolled in the Boston studies were given intramuscular

ceftriaxone. There is some concern that performing a lumbar puncture in a

bacteremic patient may lead to meningitis [93,94], and published recommendations

state that parenteral antibiotics should be ‘‘considered’’ if a lumbar puncture is

performed [66].

The results of these tests help to risk-stratify these young children. The WBC

count is considered abnormal if the count is � 15,000/mm3 or � 5000/mm3 and

the band- to-neutrophil ratio is � 0.2. The urine is considered abnormal if the

urine dipstick is positive for nitrite or leukocyte esterase; or there are � 5 WBC/hpf

on microscopy; or organisms are seen on a Gram-stained sample of un-

centrifuged urine. If obtained, there should be fewer than 5 WBC/hpf on the

stool specimen, no evidence of pneumonia on chest x-ray, and fewer than

8 WBC/mm3 and no organisms on Gram stain of the cerebrospinal fluid [66].

Of note, however, one recent study reported that four of 8300 children who

underwent CSF analysis had bacterial meningitis and � 8 WBC/mm3 in the

CSF [95].

The presence of a documented viral infection lowers but does not eliminate

the likelihood of a serious bacterial infection in this age group. Young infants

classified as high-risk patients using the Rochester criteria who had documented

viral infection (enterovirus, respiratory virus, rotavirus, and herpesvirus) were at

lower risk for SBI compared with patients who did not have an identified source

(4.2% versus 12.3%) [96]. Similarly, a subgroup analysis of 187 febrile infants

28 to 60 days old showed a significantly lower rate of SBI in RSV-positive

patients compared with RSV-negative patients (5.5% versus 11.7%) [75], con-

firming the results of similar studies in young infants who had bronchiolitis.

Most of these bacterial infections were urinary tract infections [97,98]. Patients

less than 90 days old who have enteroviral infections have a rate of concurrent

serious bacterial infections (mostly UTI) of 7% [99].

Treatment and disposition of the febrile young infant

Assuming that the patient is an otherwise healthy term infant who appears to

be well and who does not have any lab abnormalities, outpatient management

may be considered. If the patient undergoes a reliable follow-up within 24 hours,

the parents have a way of immediately accessing health care if there is a change

in the patient’s condition, and the parents and the primary care physician

understand and agree with this plan of care, then the patient may be discharged

home. The use of ceftriaxone, 50 mg/kg IVor IM, before discharge is acceptable,

as is withholding antibiotics in these low-risk patients. Patients who did not

undergo lumbar puncture in the ED should not receive antibiotics because this

will confound the evaluation for meningitis if the patient is still febrile on follow-

up examination. Close follow-up reevaluation must be assured before discharge.

For those patients who have abnormal test results or who appear to be ill,

antibiotic therapy and hospitalization are warranted. Ceftriaxone, 50 mg/kg IM or

IV (100 mg/kg if meningitis is suspected), is commonly used for these patients.


Additional antibiotics should be considered in select circumstances (eg,

ampicillin or vancomycin for suspected infection by Listeria, gram-positive

cocci, or enterococcus). Some studies suggest that patients in this age group who

have urinary tract infections may be treated on an outpatient basis [100,101];

however, there are no prospective studies with a large number of young infants

that address this question.

Older infants and toddlers: 3 to 36 months old

A temperature of � 38.08C defines a fever, and in younger children, this

temperature is the usual threshold beyond which diagnostic testing is initiated.

However, in febrile children between 3 and 36 months old (some studies extend

this group to include 2-month-old infants), a temperature of � 39.08C is com-

monly used as the threshold temperature for initiating further evaluation. This

higher temperature cutoff is used because of the increasing risk of occult bac-

teremia with increasing temperatures [40]. Large studies of occult bacteremia,

widely referenced in the medical literature, use this temperature as the study entry

criteria [25,26,102].

Evaluation of the child 3 to 36 months old

The history is often helpful in this age group. Patients are more likely to be

able to communicate complaints, and the physical examination is more in-

formative. Clinical assessment as to whether a child appears to be well, ill, or

toxic is important. A well appearance does not completely exclude bacteremia

[103], but children who appear toxic are much more likely to have serious illness

compared with ill- or well-appearing children (92% versus 26% versus 3%, re-

spectively) [104]. Many bacterial infections can be identified by history and

physical examination alone, but some infections may be occult. The serious

bacterial infections that may not be clinically apparent are bacteremia, urinary

tract infection, and pneumonia. If no focal source of infection is identified and the

cause is not believed to be viral, then diagnostic testing in this age group is

undertaken for the purposes of identifying these occult bacterial infections.

Occult bacteremia

In the era before universal PCV7 vaccination, the pathogen that most com-

monly caused occult bacteremia was S pneumoniae [25,26]. The children at

greatest risk for pneumococcal bacteremia are children between 6 and 24 months

old. There has been much controversy about the role of blood testing in the

evaluation of the febrile child, specifically regarding the value of blood testing in

the identification of occult bacteremia. There is an increased risk of bacteremia

ishimine178

with an increasing white blood cell count [26,105,106], but the sensitivity and

specificity of a white blood cell count � 15,000/mm3 is only 80% to 86% and

69% to 77%, respectively. An absolute neutrophil count (ANC) of � 10,000/mm3

is a stronger predictor of occult bacteremia than an elevated white blood cell

count. Eight percent of patients who have an ANC � 10,000/mm have occult

pneumococcal bacteremia, whereas 0.8% of patients who have an ANC

� 10,000/mm3 have occult pneumococcal bacteremia [40]. Nevertheless, using

an elevated WBC or ANC as a surrogate marker for occult bacteremia means that

many patients will unnecessarily receive antibiotics.

The shifting epidemiology of bacteremia has prompted cost-effectiveness

analyses of various management strategies. Using pre-PCV7 data, Lee and col-

leagues [107] analyzed five strategies for the 3- to 36-month-old febrile child

who did not have an identifiable source of infection. Using a bacteremia preva-

lence rate of 1.5%, the authors concluded that the most cost-efficient strategy was

to obtain CBCs and to selectively send blood cultures and treat patients

empirically for WBC counts N15,000/mm3. In their sensitivity analysis, the

authors found that when the prevalence rate of pneumococcal bacteremia dropped

to 0.5%, then clinical judgment (eg, the patient who was deemed to be at low risk

clinically for occult pneumococcal bacteremia received no testing) was a more

cost-effective strategy.

The role of antibiotics in children believed to be at high-risk for bacteremia

is controversial as well. There is currently no way of prospectively identifying

bacteremic patients, and practically, this means that at the time of the ED or office

visit, many febrile children who are at risk for bacteremia must be treated to

prevent a single serious bacterial infection. The use of both amoxicillin [108] and

ceftriaxone [102,105] appears to shorten the duration of fever in bacteremic

febrile children. However, there is a paucity of randomized, placebo-controlled

data demonstrating that the use of either oral or parenteral antibiotics prevents

significant, adverse infectious sequelae in these children. One study compared

amoxicillin with placebo for the treatment of febrile children and showed no

difference in the rates of subsequent focal infection [108]. Another retrospective

study demonstrated that, in patients ultimately found to have bacteremia, treat-

ment with oral or parenteral antibiotics reduced persistent fever, persistent bac-

teremia, and hospital admission [109]. A subsequent meta-analysis has shown

that, although ceftriaxone prevents serious bacterial infection in patients with

proven occult bacteremia, 284 patients at risk for bacteremia would need to be

treated with antibiotics to prevent one case of meningitis [110]. Although oral

antibiotics also decrease the risk of SBI in patients with occult bacteremia caused

by S pneumoniae, it is unclear whether antibiotics reduce the risk of meningitis in

these patients [111]. Additionally, there is no apparent difference in rates of

serious bacterial infection in patients with occult pneumococcal bacteremia

who are treated with oral versus parenteral antibiotics [112]. Complicating this

analysis is the fact that in a majority of patients with pneumococcal bactere-

mia, the bacteremia will resolve spontaneously [25]. Focal infections develop in

17% of bacteremic children [25], and 2.7% to 5.8% of patients with occult


pneumococcal bacteremia develop meningitis [111,113]. These analyses were

conducted on data obtained in the pre-PCV7 era, and it is likely, with the

significant decrease in invasive pneumococcal disease, that many more febrile

patients will need to be treated to prevent SBI.

There are relatively few data on occult bacteremia in the post-PCV7 era. In

one retrospective cohort study of pediatric emergency department patients, three

of 329 blood cultures in children between 2 to 36 months old were positive for

S pneumoniae. One patient was infected with a nonvaccine serotype, one was not

immunized with PCV7, and a third patient was infected with an unknown

serotype [114].

Although pneumococcus has been the most common cause of occult bac-

teremia, other causes of bacteremia can be occult as well. Salmonella causes 4%

of occult bacteremia, occurring in 0.1% of all children 3 to 36 months old who

have temperatures � 39.08C [25,26,102], and whereas the majority of patients

with Salmonella bacteremia have gastroenteritis, 5% will have primary bac-

teremia [115]. One large retrospective study of non-typhi Salmonella bacteremia

in children showed that 54% of bacteremic children had a temperature � 39.08Cand a median WBC count of 10,000/mm3. These children had a 41% rate of

persistent bacteremia on follow-up cultures, and the rates of persistent bacter-

emia were the same in patients who were treated with antibiotics at the initial visit

and those who were not. Among immunocompetent patients, 2.5% of patients

with Salmonella bacteremia had focal infections, and no difference in rates of

focal infection were noted in children older and younger than 3 months of

age [116].

Meningococcal infections are infrequent causes of bacteremia but are as-

sociated with high rates of morbidity and mortality. Combining the data from

Boston and Philadelphia occult bacteremia studies, 0.02% of children who ap-

peared to be nontoxic and had temperatures � 39.08C had meningococcal

disease [25,26]. Usually, these patients are overtly sick; however, 12% to 16%

of patients with meningococcal disease have unsuspected infection [117,118].

Although there is an association between younger age and elevated band count

with meningococcal disease, the positive predictive values of these variables are

quite low, given the low prevalence of this disease, and authors of one large

meningococcal disease study believe that routine screening for all young febrile

children with CBCs for meningococcal bacteremia is not useful [117]. Patients

who had unsuspected meningococcal disease who were treated empirically with

antibiotics had fewer complications than patients who were untreated, but there

were no differences in rates of permanent sequelae or death [119]. However,

testing and empiric treatment may be warranted for children at higher risk for

meningococcal disease. Risk factors for meningoccal bacteremia include contact

with patients with meningoccal disease, periods of meningoccal disease out-

breaks, and presence of fever and petechiae (although the majority of children

with fever and petechiae do not have invasive bacterial disease) [120–122]. A

new tetravalent meningococcal conjugate vaccine was licensed for use in the

United States in 2005. Although clinical trials in infants and young children are in

ishimine180

progress, this vaccine has been licensed and recommended for routine admin-

istration only in children 11 years old and older [123].

Children who have positive blood cultures need to be reexamined. A patient

who appears ill needs a repeat blood culture, lumbar puncture, intravenous

antibiotics, and hospital admission. Patients with pneumococcal bacteremia who

are afebrile on repeat evaluation can be followed on an outpatient basis [124]

after repeated blood cultures and antibiotics. Children who have pneumococcal

bacteremia and who are persistently febrile need repeat blood cultures and

generally should undergo lumbar puncture and require hospital admission. The

treatment and disposition for well-appearing children with Salmonella bacteremia

are less clear, but patients with meningococcal bacteremia should be hospitalized

for parenteral antibiotics [106].

Contaminated blood cultures are common, and in younger children, the rate

of contaminated cultures frequently exceeds the rate of true positive cultures

[25,26,114,125,126]. Although the average cost to the patient of a false-positive

blood culture is rather small [127], false-positive blood cultures lead to further

testing, use of antibiotics, and hospitalizations [128], along with the attendant

iatrogenic complications [129]. The rates of blood culture contamination decline

when cultures are drawn from a separate site rather than through a newly inserted

intravenous catheter [126].

Given the observed decline in invasive pneumococcal disease, the relative

infrequency of meningococcemia and Salmonella bacteremia, and the limited

value of the white blood cell count in predicting the latter two diseases, the need

for routine CBC, blood cultures, and empiric antibiotics have been called into

question in fully immunized children [130,131]. Baraff, the author of the com-

monly referenced fever algorithms [66,132], has recently stated that children

who have received three does of vaccine are at sufficiently low risk that they do

not need blood testing or antibiotics and that patients who have received only two

doses of the Hib and PCV7 vaccines are not at any significant risk for occult

bacteremia [133]. It is reasonable to address parental preferences when devising a

‘‘risk-minimizing’’ versus a ‘‘test-minimizing’’ [134] approach to these children

because parental perceptions and preferences regarding risk may differ from

those of the treating clinician.

Occult urinary tract infection

UTIs are common sources of fever in young children, and children are at risk

for permanent renal damage from UTIs. In older children, historical and ex-

amination features such as dysuria, urinary frequency, and abdominal and flank

pain may suggest urinary tract infection. However, in young children, symptoms

are usually nonspecific. Although the overall prevalence in children is 2% to 5%

[135–137], certain subgroups of children are at higher risk for UTIs. Whites,

girls, uncircumcised boys, no alternative source of fever, and temperatures

� 39.08C were associated with a higher risk; 16% of white girls less than 2 years


old with temperatures �39.08C and fever without source had urinary tract

infections [135,136]. UTIs were found in 2.7% to 3.5% of febrile children, even

when there were other potential sources of fever (eg, gastroenteritis, otitis media,

upper respiratory tract infection, and nonspecific rash) [135,136].

Based on these prevalence data, a clinical decision rule was derived and

validated for febrile girls less than 24 months of age. Urine testing is indicated if

two or more of the following risk factors are present: age less than 12 months,

fever for 2 or more days, temperature � 39.08C, white, and no alternative source

of fever [138]. This rule has a sensitivity of 95% to 99% and a false-positive rate

69% to 90% in detecting girls with UTI [138,139]. No similar clinical decision

rules exist for boys, but because the prevalence in boys less than 6 months old is

2.7% [136], urine should be collected in all boys in this age group. The preva-

lence of UTIs in uncircumcised boys is 8 to 9 times higher than circumcised boys,

so uncircumcised boys younger than 12 months old should also undergo urine

testing [136,140,141].

Urine culture is the gold standard for the diagnosis of urinary tract infection,

but results are not immediately available. Several rapid urine tests have very good

sensitivity for detecting UTIs. Enhanced urinalysis (�10 WBC/hpf or bacteria on

Gram stained, uncentrifuged urine) [71,142] or a combination of � 10 WBC/hpf

and bacteriuria (on either centrifuged or uncentrifuged urine) [143] are both

excellent screening tests. The more readily available urine dipstick (positive for

either leukocyte esterase or nitrites) has a sensitivity of 88% [71]. Importantly,

however, because no rapid screening test detected all UTIs, urine cultures should

be ordered on all of these patients [74]. Any positive test results from a rapid test

should lead to a presumptive diagnosis of a urinary tract infection, and antibiotic

treatment should be initiated. Most patients with urinary tract infection who

appear well can be treated on an outpatient basis. Empiric antibiotic therapy

should be tailored to local bacterial epidemiology, but reasonable outpatient medi-

cations include cefixime (8 mg/kg twice on the first day of treatment, then

8 mg/kg/d, starting from the second day) or cephalexin (25–100 mg/kg/d

divided into four doses). The duration of therapy should be from 7 to 14 days.

Occult pneumonia

Young children commonly develop pneumonia, and the most common patho-

gens are viruses and (based on pre-PCV7 data) S pneumoniae [144]. The diagno-

sis of pneumonia based on clinical examination can be difficult [145]. Multiple

attempts have been made at deriving clinical decision rules for the accurate

diagnosis of pneumonia, but none has been successfully validated [146–148].

The presence of any pulmonary findings on examination (eg, tachypnea, crackles,

respiratory distress, or decreased breath sounds) increases the likelihood of pneu-

monia, and conversely, the absence of these findings decreases the likelihood of

pneumonia [149–151]. The role of pulse oximetry in detecting pneumonia is

unclear [152,153], and although the chest radiograph is often believed to be the

ishimine182

gold standard, there is variability in the interpretation of radiographs even by

pediatric radiologists [154]. Radiographic findings cannot be used to distinguish

reliably between bacterial and nonbacterial causes [155,156]. In one South Afri-

can study, chest radiographs did not affect the clinical outcome in children meet-

ing the World Health Organization definition of pneumonia [157].

Some cases of pneumonia are likely to be clinically occult. Bachur and

colleagues [158] found that 19% to 26% of children younger than 5 years old

who had a temperature of �39.08C, a WBC count �20,000/mm3, and no other

source or only a ‘‘minor’’ bacterial source on examination had a pneumonia in-

fection as seen on a chest radiograph. A clinical policy by the American College

of Emergency Physicians states that a chest radiograph should be considered in

children older than 3 months who have a temperature �398C and a WBC count

�20,000/mm3 and that a chest radiograph is usually not indicated in febrile

children older than 3 months who have a temperature �398C without clinical

evidence of acute pulmonary disease [90]. The British Thoracic Society similarly

recommends that a chest radiograph should be considered in children younger

than 5 years old who have a temperature �398C caused by an unclear source of

infection [159]. These recommendations may change based on the decline of the

prevalence of pneumococcal pneumonia [160]. No decision rules exist for

pediatric pneumonia that help with disposition decisions in children who have

pneumonia, but the majority of patients are treated on an outpatient basis. Both

amoxicillin (80 mg/kg/d divided twice or three times daily) and macrolide anti-

biotics (eg, azithromycin, 10 mg/kg by mouth on the first day, then 5 mg/kg/d

for 4 more days) are acceptable. Treatment duration is usually from 7 to 10 days

(with the exception of azithromycin), but no definitive evidence supports a spe-

cific duration of therapy [159].

Future directions and questions

The pneumococcal vaccine has already had a significant impact on the epi-

demiology of bacterial infection in young children, and this vaccine has already

seems to have had some impact on the practice patterns of pediatricians.

Pediatricians who were surveyed were found to order fewer blood and urine

tests and were less likely to prescribe antibiotics in a hypothetical scenario of an

8-month-old febrile but otherwise healthy infant when the child had been fully

immunized with PCV7 compared with a nonimmunized child [161]. Some

authors have begun advocating a less aggressive approach to the evaluation of

the immunized febrile child, given the decline in invasive pneumococcal disease

with PCV7 [131,133]. Other investigators, however, are urging caution before

changing evaluation and management strategies, postulating that invasive pneu-

mococcal disease will persist for several reasons: not all serotypes are covered by

vaccine, some children will not be able to mount an adequate immune response

to form protective antibodies, and some children still will be incompletely im-

munized [162].


Other questions regarding PCV7 have arisen. Among the seven serotypes,

the amount of disease reduction is variable [34–36]. Furthermore, although the

overall rate of invasive pneumococcal disease is lower, there is an increase in the

percentage of invasive pneumococcal disease caused by nonvaccine serogroups

[33–36]. The clinical implications of this serotype replacement remains unclear

but will depend on the capacity of the PCV7 vaccine to protect against these

noncovered serotypes as well as the virulence of the nonvaccine strains. Pneu-

mococcal conjugate vaccines intended to cover nine and 11 serotypes are in

development [163]. Another question that remains unanswered is the duration of

protection afforded to patients who are immunized. Finally, the approach to the

patient who is not fully immunized is still unclear. Partial immunization likely

provides some protection against pneumococcus; the majority of patients in the

post-surveillance PCV7 studies were not fully immunized (ie, three vaccinations),

but there was still a decline in invasive pneumococcal disease [33].

Despite the use of the PCV7 vaccine, patients will still develop bacteremia,

and there will be still be a need for better tests to diagnose invasive bacterial

disease. Several additional tests are being studied as potential surrogate markers

for bacterial disease in young children: procalcitonin (not yet available in the

United States), C-reactive protein, and interleukin-6 [164–171].

Summary

Most children 0 to 36 months of age who have fever without an obvious

source have viral infections, but certain subsets of febrile children are at higher

risk for more serious bacterial disease. The child who appears to be toxic, re-

gardless of age, needs a comprehensive work-up, antibiotic coverage, and

admission to the hospital. Generally, this entails a complete blood count with

differential, blood culture, urinalysis and urine culture, lumbar puncture with

cerebrospinal fluid analysis, Gram stain and culture, and, when indicated, chest

radiographs and stool studies. These patients should receive broad-spectrum

parenteral antibiotics before hospital admission. The febrile neonate (0–28 days

old) is at high risk for serious bacterial infection, even with benign examination

and normal screening laboratory results. Therefore, these patients also need a

complete blood count with differential, blood culture, urinalysis and urine cul-

ture, lumbar puncture with cerebrospinal fluid analysis, Gram stain and culture,

and, when indicated, chest radiographs and stool studies. Febrile neonates should

receive empiric antibiotic coverage, typically with ampicillin (50 mg/kg IV, or

100 mg/kg if meningitis is suspected) and cefotaxime (50 mg/kg IV, or 100 mg/

kg if meningitis is suspected) or gentamicin (2.5 mg/kg IV).

The febrile young infant (1–3 months old) is also at significant risk for

bacterial infection. These patients need complete blood counts, blood cultures,

urinalyses and urine cultures. A lumbar puncture with cerebrospinal fluid analy-

sis, Gram stain, and culture should be strongly considered because laboratory

ishimine184

tests such as the white blood cell count are inaccurate in predicting which patients

have meningitis. When they are clinically indicated, chest radiographs and stool

studies should be obtained as well. If any of these test findings are abnormal

(including peripheral WBC � 15,000/mm3 or � 5000/mm3, band-to-neutrophil

ratio � 0.2, a urine dipstick test positive for nitrite or leukocyte esterase, or

� 5 WBCs/hpf, or organisms seen on Gram stain; cerebrospinal fluid with

� 8 WBC/mm3 or organisms on Gram stain; or � 5 WBC/hpf on the stool speci-

men or evidence of pneumonia on a chest radiograph), these patients should re-

ceive ceftriaxone (50 mg/kg IVor IM, or 100 mg/kg IV if meningitis is suspected)

Temperature ≥38.0° and age 0-3 months

Age <28 days or toxic appearance

1. Blood culture 2. Rapid urine testing 2. Urine culture 4. Cerebrospinal fluid Gram stain and culture 5. Chest x-ray and stool studies if indicated 6. Peripheral WBC with differential 7. Consider HSV studies8. IV antibiotics9. Hospital admission

Baseline high-risk

1. Peripheral WBC with differential 2. Blood culture 3. Rapid urine testing 4. Urine culture 6. Chest x-ray and stool studies ifindicated

1. Peripheral WBC with differential 2. Blood culture 3. Rapid urine testing 4. Urine culture 5. Cerebrospinal fluid Gram stain and culture 6. Chest x-ray and stool studies if indicated

Abnormallabs or x-ray

1. Cerebrospinal fluid Gramstain and culture if not initially performed 2. Ceftriaxone 50 mg/kg IV or IM 3. Hospital admission

1. Follow-up assured in 24 hours 2. Adequate social situation (e.g., access to telephone and transportation) 3. Parents and primary care physician agreeable to outpatient approach 4. Consider ceftriaxone 50 mg/kg IV /IM but only iflumbar puncture is performed

Discharge

Age 29 days - < 2 months

A

B

C

D

Yes

No

Age 2-3 months

Option 1 Option 2

E

Yes

No

No

No

Yes

Yes


and should be admitted to the hospital. If these initial laboratory results are normal,

a patient can be discharged if follow-up within 24 hours (or sooner if clinically

worse) can be assured. The administration of ceftriaxone, 50 mg/kg IV or IM,

should be considered if a lumbar puncture is performed, but if a lumbar puncture is

not performed, antibiotics should be withheld. If a patient is 2 to 3 months old and

the practitioner is comfortable with pediatric assessment skills, these children can

be treated similarly to older febrile children.

The older infant or toddler (3–36 months old) who has a temperature of

� 39.08C may be treated more selectively. In this age group, if no febrile source

is identified definitively, a catheterized urine specimen for evaluation (dipstick,

urinalysis, microscopy, or Gram stain) and urine culture should be obtained in

girls less than 2 years old, if two or more of the following risk factors are present:

age less than 12 months old, fever for 2 or more days, temperature � 39.08C,white, and no alternative source of fever. All boys younger than 6 months old and

all uncircumcised boys younger than 12 months old should also have catheterized

urine sent for rapid urine testing and culture. Based on pre-PCV7 data, the most

cost-effective approach to the child who has not had at least three PCV7 doses is

to obtain a CBC. If the WBC count is � 15,000/mm 3, a blood culture should be

ordered and the administration of ceftriaxone should be considered. Other options

(eg, blood culture only or CBC and blood culture with selective antibiotic ad-

ministration) are reasonable. However, in nontoxic children who have had three

PCV7 immunizations and who are not at risk for meningococcal disease, some

practitioners believe that obtaining any blood work is unnecessary. The current

Fig. 1. (A) Urine testing can be accomplished either by microscopy, Gram stain, or urine dipstick.

Chest radiographs are indicated in patients with hypoxia, tachypnea, abnormal lung sounds, or

respiratory distress. Stool studies are indicated in patients with diarrhea. Herpes simplex virus testing

should be considered in the presence of risk factors (see text for details). HSV testing is best

accomplished by polymerase chain reaction or viral culture. Neonates should receive both ampicillin

(50 mg/kg IV, or 100 mg/kg IV if meningitis is suspected) and cefotaxime (50 mg/kg, or 100 mg/kg IV

if meningitis is suspected) or gentamicin (2.5 mg/kg IV). Additionally, neonates with findings sug-

gestive of HSV infection should receive acyclovir (20 mg/kg IV). Older children should receive

ceftriaxone (50 mg/kg IV, or 100 mg/kg IV if meningitis is suspected). A WBC count with differen-

tial may be ordered, but the results should not dissuade the clinician from pursuing a full evaluation

and treatment with antibiotics. (B) Young patients who have increased underlying risk include chil-

dren who were premature, had prolonged hospital stays after birth, those with underlying medical

conditions, patients with indwelling medical devices, fever lasting longer than 5 days, or patients

already on antibiotics. (C) Urine testing can be accomplished either by microscopy, Gram stain, or

urine dipstick. Chest radiographs are indicated in patients with hypoxia, tachypnea, abnormal lung

sounds, or respiratory distress. Stool studies are indicated in patients with diarrhea. (D) Abnormal

laboratory findings: peripheral WBC count � 5,000/mm3 or � 15,000/mm3 or band-to-neutrophil

ratio � 0.2; urine testing, � 5 WBC/hpf, bacteria on Gram stain, or positive leukocyte esterase or

nitrite; cerebrospinal fluid, � 8 WBC/mm3 or bacteria on Gram stain; stool specimen, � 5 WBC/hpf;

and chest radiograph, infiltrate detected. (E) Administering ceftriaxone (50 mg/kg IV or IM) is

optional but should only be considered in patients who have undergone lumbar puncture. Patients

who have not undergone lumbar puncture should not get ceftriaxone. (Adapted from Baraff L.

Management of fever without source in infants and children. Ann Emerg Med 2000;36(6):602–14.)

ishimine186

evidence suggests that this may become a reasonable approach, but studies

addressing this specific approach have not yet been published (Figs. 1 and 2).

Finally, it is critically important to recognize that there is no combination of

clinical assessment and diagnostic testing that will successfully identify all

patients with serious infection at the time of initial presentation. Therefore, the

importance of timely reassessment cannot be overemphasized, and caretakers

must be instructed to return to the ED or the office immediately for any

deterioration in the child’s condition. While strategies such as that described

above may help guide the evaluation and treament of febrile young infants,

Age 3-36 months Healthy without underlying medical conditions

Nontoxic appearance and no obvious source 1. No diagnostic testing required 2. Discharge home with follow-up in 48 hours if fever persists 3. Reevaluation if condition worsens

Evaluate for occult infection

Occult pneumonia 1. Obtain CXR if patient has

hypoxia, tachypnea, respiratory distress, abnormal breath sounds

2. Consider CXR if no other source identified and WBC >20,000/mm3 (if obtained)

Occult UTI 1. Obtain rapid urine testing and

culture in girls <24 months if 1 risk factor present:

• Fever ≥2 days • Age < 12 months • White race • No alternative source of fever 2. Strongly consider rapid urine

testing and culture for uncircumcised boys <12m and circumcised boys <6m

Rapid urine test positive?

1. Outpatient oral antibiotics (e.g., cefixime, cephalexin) 2. Consider giving first dose of parenteral antibiotics (e.g., ceftriaxone) in ED or office

Findings suggestive of pneumonia?

1. Assess clinical stability for discharge 2 Ensure ability to obtain follow-up care 2. Follow-up in 24-48 hours for persistent

symptoms 3. Immediate follow-up for worsening condition 4. Immediate follow-up for positive blood culture 5. Discharge home

1. Outpatient oral antibiotics (e.g., amoxicillin, azithromycin) 2. Consider giving first dose of parenteral antibiotics (e.g., ceftriaxone) in ED or office

Occult Bacteremia 1. Increased risk with • Temp ≥40°C • WBC > 15,000/mm3 or

ANC >10,000/mm3

• Age 6-24 months • Contacts with

meningococcal disease • Petechiae • Prolonged gastroenteritis

Several acceptable options:

Option 1 • CBC with diff • If WBC >15K, blood

culture and ceftriaxone

Option 2 • Blood culture

Option 3 For patients with ≥3 PCV7 doses: • No blood testing

Temp ≥39°C

Yes No

Yes No

No

Yes

Fig. 2. Algorithm for treating children aged 3 to 36 months old (may be used for patients 2 to 3 months

old as well; see text). (Adapted from Baraff L. Management of fever without source in infants and

children. Ann Emerg Med 2000;36(6):602–14.)


no single approach can capture the nuances of all febrile young patients.

Therefore, this approach should serve as an adjunct to, and not a replacement

for clinician judgment.

References

[1] Nelson DS, Walsh K, Fleisher GR. Spectrum and frequency of pediatric illness presenting to

a general community hospital emergency department. Pediatrics 1992;90(1 Pt 1):5–10.

[2] Krauss BS, Harakal T, Fleisher GR. The spectrum and frequency of illness presenting to a

pediatric emergency department. Pediatr Emerg Care 1991;7(2):67–71.

[3] McCaig LF, Burt CW. National Hospital Ambulatory Medical Care Survey: 2002 emergency

department summary. Adv Data 2004;340:1–34.

[4] Wittler RR, Cain KK, Bass JW. A survey about management of febrile children without source

by primary care physicians. Pediatr Infect Dis J 1998;17(4):271–7 [discussion: 7–9].

[5] Baraff LJ, Schriger DL, Bass JW, et al. Management of the young febrile child: commentary on

practice guidelines. Pediatrics 1997;100(1):134–6.

[6] Belfer RA, Gittelman MA, Muniz AE. Management of febrile infants and children by pediatric

emergency medicine and emergency medicine: comparison with practice guidelines. Pediatr

Emerg Care 2001;17(2):83–7.

[7] Isaacman DJ, Kaminer K, Veligeti H, et al. Comparative practice patterns of emergency

medicine physicians and pediatric emergency medicine physicians managing fever in young

children. Pediatrics 2001;108(2):354–8.

[8] Kramer MS, Shapiro ED. Management of the young febrile child: a commentary on recent

practice guidelines. Pediatrics 1997;100(1):128–34.

[9] Mackowiak PA. Concepts of fever. Arch Intern Med 1998;158(17):1870–81.

[10] Craig JV, Lancaster GA, Taylor S, et al. Infrared ear thermometry compared with rectal

thermometry in children: a systematic review. Lancet 2002;360(9333):603–9.

[11] Craig JV, Lancaster GA, Williamson PR, et al. Temperature measured at the axilla compared

with rectum in children and young people: systematic review. BMJ 2000;320(7243):1174–8.

[12] Jean-Mary MB, Dicanzio J, Shaw J, et al. Limited accuracy and reliability of infrared axil-

lary and aural thermometers in a pediatric outpatient population. J Pediatr 2002;141(5):

671–6.

[13] Gittelman MA, Mahabee-Gittens EM, Gonzalez-del-Rey J. Common medical terms defined by

parents: are we speaking the same language? Pediatr Emerg Care 2004;20(11):754–8.

[14] Banco L, Veltri D. Ability of mothers to subjectively assess the presence of fever in their

children. Am J Dis Child 1984;138(10):976–8.

[15] Hooker EA, Smith SW, Miles T, King L. Subjective assessment of fever by parents: compari-

son with measurement by noncontact tympanic thermometer and calibrated rectal glass mer-

cury thermometer. Ann Emerg Med 1996;28(3):313–7.

[16] Graneto JW, Soglin DF. Maternal screening of childhood fever by palpation. Pediatr Emerg

Care 1996;12(3):183–4.

[17] Crocetti M, Moghbeli N, Serwint J. Fever phobia revisited: have parental misconceptions

about fever changed in 20 years? Pediatrics 2001;107(6):1241–6.

[18] Schmitt BD. Fever phobia: misconceptions of parents about fevers. Am J Dis Child 1980;

134(2):176–81.

[19] Grover G, Berkowitz CD, Lewis RJ, et al. The effects of bundling on infant temperature.

Pediatrics 1994;94(5):669–73.

[20] Pantell RH, Newman TB, Bernzweig J, et al. Management and outcomes of care of fever in

early infancy. JAMA 2004;291(10):1203–12.

[21] McGowan Jr JE, Bratton L, Klein JO, et al. Bacteremia in febrile children seen in a ‘‘walk-in’’

pediatric clinic. N Engl J Med 1973;288(25):1309–12.

ishimine188

[22] Bisgard KM, Kao A, Leake J, et al. Haemophilus influenzae invasive disease in the United

States, 1994–1995: near disappearance of a vaccine-preventable childhood disease. Emerg

Infect Dis 1998;4(2):229–37.

[23] Wenger JD. Epidemiology of Haemophilus influenzae type b disease and impact of Hae-

mophilus influenzae type b conjugate vaccines in the United States and Canada. Pediatr Infect

Dis J 1998;17(9 Suppl):S132–6.

[24] Schuchat A, Robinson K, Wenger JD, et al. Bacterial meningitis in the United States in 1995:

Active Surveillance Team. N Engl J Med 1997;337(14):970–6.

[25] Alpern ER, Alessandrini EA, Bell LM, et al. Occult bacteremia from a pediatric emergency

department: current prevalence, time to detection, and outcome. Pediatrics 2000;106(3):505–11.

[26] Lee GM, Harper MB. Risk of bacteremia for febrile young children in the post-Haemophilus

influenzae type b era. Arch Pediatr Adolesc Med 1998;152(7):624–8.

[27] Robinson KA, Baughman W, Rothrock G, et al. Epidemiology of invasive Streptococcus

pneumoniae infections in the United States, 1995–1998: opportunities for prevention in the

conjugate vaccine era. JAMA 2001;285(13):1729–35.

[28] Whitney CG, Farley MM, Hadler J, et al. Increasing prevalence of multidrug-resistant

Streptococcus pneumoniae in the United States. N Engl J Med 2000;343(26):1917–24.

[29] Kaplan SL, Mason Jr EO, Wald E, et al. Six year multicenter surveillance of invasive

pneumococcal infections in children. Pediatr Infect Dis J 2002;21(2):141–7.

[30] American Academy of Pediatrics. Pneumococcal infections. In: Pickering L, editor. Red book:

2003 report of the Committee on Infectious Diseases. 26th edition. Elk Grove Village (IL)7

American Academy of Pediatrics; 2003. p. 490–500.

[31] Wise RP, Iskander J, Pratt RD, et al. Postlicensure safety surveillance for 7-valent pneu-

mococcal conjugate vaccine. JAMA 2004;292(14):1702–10.

[32] Black S, Shinefield H, Fireman B, et al for the Northern California Kaiser Permanente Vaccine

Study Center Group. Efficacy, safety and immunogenicity of heptavalent pneumococcal con-

jugate vaccine in children. Pediatr Infect Dis J 2000;19(3):187–95.

[33] Black S, Shinefield H, Baxter R, et al for the in Northern California Kaiser Permanente Vaccine

Center Group. Postlicensure surveillance for pneumococcal invasive disease after use of

heptavalent pneumococcal conjugate vaccine. Pediatr Infect Dis J 2004;23(6):485–9.

[34] Hsu K, Pelton S, Karumuri S, et al. Population-based surveillance for childhood invasive

pneumococcal disease in the era of conjugate vaccine. Pediatr Infect Dis J 2005;24(1):17–23.

[35] Whitney CG, Farley MM, Hadler J, et al. Decline in invasive pneumococcal disease after

the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med 2003;348(18):

1737–46.

[36] Kaplan SL, Mason Jr EO, Wald ER, et al. Decrease of invasive pneumococcal infections in

children among 8 children’s hospitals in the United States after the introduction of the 7-valent

pneumococcal conjugate vaccine. Pediatrics 2004;113(3 Pt 1):443–9.

[37] Alpern E, Henretig F. Fever. In: Fleisher G, Ludwig S, Henretig F, et al, editors. Textbook of

pediatric emergency medicine. 5th edition. Philadelphia7 Lippincott Williams & Wilkins; 2006.

p. 295–306.

[38] Finkelstein JA, Christiansen CL, Platt R. Fever in pediatric primary care: occurrence, man-

agement, and outcomes. Pediatrics 2000;105(1 Pt 3):260–6.

[39] Roberts KB. Young, febrile infants: a 30-year odyssey ends where it started. JAMA 2004;

291(10):1261–2.

[40] Kuppermann N, Fleisher G, Jaffe D. Predictors of occult pneumococcal bacteremia in young

febrile children. Ann Emerg Med 1998;31(6):679–87.

[41] Stanley R, Pagon Z, Bachur R. Hyperpyrexia among infants younger than 3 months. Pediatr

Emerg Care 2005;21(5):291–4.

[42] Teach SJ, Fleisher GR for the Occult Bacteremia Study Group. Duration of fever and its

relationship to bacteremia in febrile outpatients three to 36 months old. Pediatr Emerg Care

1997;13(5):317–9.

[43] Li SF, Lacher B, Crain EF. Acetaminophen and ibuprofen dosing by parents. Pediatr Emerg

Care 2000;16(6):394–7.


[44] McErlean MA, Bartfield JM, Kennedy DA, et al. Home antipyretic use in children brought

to the emergency department. Pediatr Emerg Care 2001;17(4):249–51.

[45] Huang SY, Greenes DS. Effect of recent antipyretic use on measured fever in the pediatric

emergency department. Arch Pediatr Adolesc Med 2004;158(10):972–6.

[46] Baker MD, Fosarelli PD, Carpenter RO. Childhood fever: correlation of diagnosis with tem-

perature response to acetaminophen. Pediatrics 1987;80(3):315–8.

[47] Baker RC, Tiller T, Bausher JC, et al. Severity of disease correlated with fever reduction in

febrile infants. Pediatrics 1989;83(6):1016–9.

[48] Torrey SB, Henretig F, Fleisher G, et al. Temperature response to antipyretic therapy in

children: relationship to occult bacteremia. Am J Emerg Med 1985;3(3):190–2.

[49] Yamamoto LT, Wigder HN, Fligner DJ, et al. Relationship of bacteremia to antipyretic therapy

in febrile children. Pediatr Emerg Care 1987;3(4):223–7.

[50] Greenes DS, Harper MB. Low risk of bacteremia in febrile children with recognizable viral

syndromes. Pediatr Infect Dis J 1999;18(3):258–61.

[51] Smitherman HF, Caviness AC, Macias CG. Retrospective review of serious bacterial infections

in infants who are 0 to 36 months of age and have influenza A infection. Pediatrics 2005;

115(3):710–8.

[52] Schutzman SA, Petrycki S, Fleisher GR. Bacteremia with otitis media. Pediatrics 1991;87(1):

48–53.

[53] Turner D, Leibovitz E, Aran A, et al. Acute otitis media in infants younger than two months of

age: microbiology, clinical presentation and therapeutic approach. Pediatr Infect Dis J 2002;

21(7):669–74.

[54] DeAngelis C, Joffe A, Willis E, et al. Hospitalization v outpatient treatment of young, febrile

infants. Am J Dis Child 1983;137(12):1150–2.

[55] DeAngelis C, Joffe A, Wilson M, et al. Iatrogenic risks and financial costs of hospitalizing

febrile infants. Am J Dis Child 1983;137(12):1146–9.

[56] Paxton RD, Byington CL. An examination of the unintended consequences of the rule-out

sepsis evaluation: a parental perspective. Clin Pediatr (Phila) 2001;40(2):71–7.

[57] Baker MD, Bell LM. Unpredictability of serious bacterial illness in febrile infants from birth

to 1 month of age. Arch Pediatr Adolesc Med 1999;153(5):508–11.

[58] Kadish HA, Loveridge B, Tobey J, et al. Applying outpatient protocols in febrile infants 1–28

days of age: can the threshold be lowered? Clin Pediatr (Phila) 2000;39(2):81–8.

[59] Pena BM, Harper MB, Fleisher GR. Occult bacteremia with group B streptococci in an out-

patient setting. Pediatrics 1998;102(1 Pt 1):67–72.

[60] Hoffman JA, Mason EO, Schutze GE, et al. Streptococcus pneumoniae infections in the

neonate. Pediatrics 2003;112(5):1095–102.

[61] Dagan R, Powell KR, Hall CB, et al. Identification of infants unlikely to have serious bacterial

infection although hospitalized for suspected sepsis. J Pediatr 1985;107(6):855–60.

[62] Dagan R, Sofer S, Phillip M, et al. Ambulatory care of febrile infants younger than 2 months of

age classified as being at low risk for having serious bacterial infections. J Pediatr 1988;112(3):

355–60.

[63] Jaskiewicz JA, McCarthy CA, Richardson AC, et al for the Febrile Infant Collaborative Study

Group. Febrile infants at low risk for serious bacterial infection–an appraisal of the Rochester

criteria and implications for management. Pediatrics 1994;94(3):390–6.

[64] Ferrera PC, Bartfield JM, Snyder HS. Neonatal fever: utility of the Rochester criteria in

determining low risk for serious bacterial infections. Am J Emerg Med 1997;15(3):299–302.

[65] Baker MD, Bell LM, Avner JR. Outpatient management without antibiotics of fever in selected

infants. N Engl J Med 1993;329(20):1437–41.

[66] Baraff L. Management of fever without source in infants and children. Ann Emerg Med

2000;36(6):602–14.

[67] Steere M, Sharieff GQ, Stenklyft PH. Fever in children less than 36 months of age: questions

and strategies for management in the emergency department. J Emerg Med 2003;25(2):149–57.

[68] Bonsu BK, Harper MB. Utility of the peripheral blood white blood cell count for identifying

sick young infants who need lumbar puncture. Ann Emerg Med 2003;41(2):206–14.

ishimine190

[69] Bonsu BK, Harper MB. Identifying febrile young infants with bacteremia: is the peripheral

white blood cell count an accurate screen? Ann Emerg Med 2003;42(2):216–25.

[70] Brown L, Shaw T, Wittlake WA. Does leucocytosis identify bacterial infections in febrile

neonates presenting to the emergency department? Emerg Med J 2005;22(4):256–9.

[71] Gorelick MH, Shaw KN. Screening tests for urinary tract infection in children: a meta-analysis.

Pediatrics 1999;104(5):e54.

[72] Shaw KN, McGowan KL, Gorelick MH, et al. Screening for urinary tract infection in infants

in the emergency department: which test is best? Pediatrics 1998;101(6):E1.

[73] Al-Orifi F, McGillivray D, Tange S, et al. Urine culture from bag specimens in young children:

are the risks too high? J Pediatr 2000;137(2):221–6.

[74] Committee on Quality Improvement, Subcommittee on Urinary Tract Infection. Practice pa-

rameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile

infants and young children. Pediatrics 1999;103(4):843–52.

[75] Levine DA, Platt SL, Dayan PS, et al. Risk of serious bacterial infection in young febrile infants

with respiratory syncytial virus infections. Pediatrics 2004;113(6):1728–34.

[76] Wadsworth SJ, Suh B. In vitro displacement of bilirubin by antibiotics and 2-hydroxybenzoyl-

glycine in newborns. Antimicrob Agents Chemother 1988;32(10):1571–5.

[77] Martin E, Fanconi S, Kalin P, et al. Ceftriaxone–bilirubin-albumin interactions in the neonate:

an in vivo study. Eur J Pediatr 1993;152(6):530–4.

[78] Robertson A, Fink S, Karp W. Effect of cephalosporins on bilirubin-albumin binding. J Pediatr

1988;112(2):291–4.

[79] Sadow KB, Derr R, Teach SJ. Bacterial infections in infants 60 days and younger: epi-

demiology, resistance, and implications for treatment. Arch Pediatr Adolesc Med 1999;153(6):

611–4.

[80] Brown JC, Burns JL, Cummings P. Ampicillin use in infant fever: a systematic review. Arch

Pediatr Adolesc Med 2002;156(1):27–32.

[81] Brown ZA, Wald A, Morrow RA, et al. Effect of serologic status and cesarean delivery

on transmission rates of herpes simplex virus from mother to infant. JAMA 2003;289(2):

203–9.

[82] Kimberlin DW, Lin CY, Jacobs RF, et al. Natural history of neonatal herpes simplex virus

infections in the acyclovir era. Pediatrics 2001;108(2):223–9.

[83] Kimberlin DW, Lin CY, Jacobs RF, et al. Safety and efficacy of high-dose intravenous acyclovir

in the management of neonatal herpes simplex virus infections. Pediatrics 2001;108(2):230–8.

[84] Kimberlin D. Herpes simplex virus, meningitis and encephalitis in neonates. Herpes 2004;

11(Suppl 2):A65–76.

[85] Kimberlin DW. Neonatal herpes simplex infection. Clin Microbiol Rev 2004;17(1):1–13.

[86] Chiu CH, Lin TY, Bullard MJ. Identification of febrile neonates unlikely to have bacterial

infections. Pediatr Infect Dis J 1997;16(1):59–63.

[87] Baker MD, Avner JR, Bell LM. Failure of infant observation scales in detecting serious illness

in febrile, 4- to 8-week-old infants. Pediatrics 1990;85(6):1040–3.

[88] Baskin MN, O’Rourke EJ, Fleisher GR. Outpatient treatment of febrile infants 28 to 89 days

of age with intramuscular administration of ceftriaxone. J Pediatr 1992;120(1):22–7.

[89] Baker MD, Bell LM, Avner JR. The efficacy of routine outpatient management without

antibiotics of fever in selected infants. Pediatrics 1999;103(3):627–31.

[90] American College of Emergency Physicians Clinical Policies Committee and Subcommittee

on Pediatric Fever. Clinical policy for children younger than three years presenting to the

emergency department with fever. Ann Emerg Med 2003;42(4):530–45.

[91] Bramson RT, Meyer TL, Silbiger ML, et al. The futility of the chest radiograph in the febrile

infant without respiratory symptoms. Pediatrics 1993;92(4):524–6.

[92] Bonsu BK, Harper MB. A low peripheral blood white blood cell count in infants younger than

90 days increases the odds of acute bacterial meningitis relative to bacteremia. Acad Emerg

Med 2004;11(12):1297–301.

[93] Shapiro ED, Aaron NH, Wald ER, et al. Risk factors for development of bacterial meningitis

among children with occult bacteremia. J Pediatr 1986;109(1):15–9.


[94] Teele DW, Dashefsky B, Rakusan T, et al. Meningitis after lumbar puncture in children with

bacteremia. N Engl J Med 1981;305(18):1079–81.

[95] Bonsu BK, Harper MB. Accuracy and test characteristics of ancillary tests of cerebrospinal

fluid for predicting acute bacterial meningitis in children with low white blood cell counts in

cerebrospinal fluid. Acad Emerg Med 2005;12(4):303–9.

[96] Byington CL, Enriquez FR, Hoff C, et al. Serious bacterial infections in febrile infants 1 to

90 days old with and without viral infections. Pediatrics 2004;113(6):1662–6.

[97] Liebelt EL, Qi K, Harvey K. Diagnostic testing for serious bacterial infections in infants aged

90 days or younger with bronchiolitis. Arch Pediatr Adolesc Med 1999;153(5):525–30.

[98] Titus MO, Wright SW. Prevalence of serious bacterial infections in febrile infants with

respiratory syncytial virus infection. Pediatrics 2003;112(2):282–4.

[99] Rittichier KR, Bryan PA, Bassett KE, et al. Diagnosis and outcomes of enterovirus infections

in young infants. Pediatr Infect Dis J 2005;24(6):546–50.

[100] Dayan PS, Hanson E, Bennett JE, et al. Clinical course of urinary tract infections in infants

younger than 60 days of age. Pediatr Emerg Care 2004;20(2):85–8.

[101] Hoberman A, Wald ER, Hickey RW, et al. Oral versus initial intravenous therapy for urinary

tract infections in young febrile children. Pediatrics 1999;104(1 Pt 1):79–86.

[102] Fleisher GR, Rosenberg N, Vinci R, et al. Intramuscular versus oral antibiotic therapy for the

prevention of meningitis and other bacterial sequelae in young, febrile children at risk for occult

bacteremia. J Pediatr 1994;124(4):504–12.

[103] Teach SJ, Fleisher GR for the Occult Bacteremia Study Group. Efficacy of an observation scale

in detecting bacteremia in febrile children three to thirty-six months of age, treated as

outpatients. J Pediatr 1995;126(6):877–81.

[104] McCarthy PL, Sharpe MR, Spiesel SZ, et al. Observation scales to identify serious illness

in febrile children. Pediatrics 1982;70(5):802–9.

[105] Bass JW, Steele RW, Wittler RR, et al. Antimicrobial treatment of occult bacteremia: a mul-

ticenter cooperative study. Pediatr Infect Dis J 1993;12(6):466–73.

[106] Kuppermann N. Occult bacteremia in young febrile children. Pediatr Clin North Am 1999;

46(6):1073–109.

[107] Lee GM, Fleisher GR, Harper MB. Management of febrile children in the age of the conjugate

pneumococcal vaccine: a cost-effectiveness analysis. Pediatrics 2001;108(4):835–44.

[108] Jaffe DM, Tanz RR, Davis AT, et al. Antibiotic administration to treat possible occult

bacteremia in febrile children. N Engl J Med 1987;317(19):1175–80.

[109] Harper MB, Bachur R, Fleisher GR. Effect of antibiotic therapy on the outcome of outpatients

with unsuspected bacteremia. Pediatr Infect Dis J 1995;14(9):760–7.

[110] Bulloch B, Craig WR, Klassen TP. The use of antibiotics to prevent serious sequelae in children

at risk for occult bacteremia: a meta-analysis. Acad Emerg Med 1997;4(7):679–83.

[111] Rothrock SG, Harper MB, Green SM, et al. Do oral antibiotics prevent meningitis and serious

bacterial infections in children with Streptococcus pneumoniae occult bacteremia? a meta-

analysis. Pediatrics 1997;99(3):438–44.

[112] Rothrock SG, Green SM, Harper MB, et al. Parenteral vs oral antibiotics in the prevention

of serious bacterial infections in children with Streptococcus pneumoniae occult bacteremia:

a meta-analysis. Acad Emerg Med 1998;5(6):599–606.

[113] Baraff LJ, Oslund S, Prather M. Effect of antibiotic therapy and etiologic microorganism on the

risk of bacterial meningitis in children with occult bacteremia. Pediatrics 1993;92(1):140–3.

[114] Stoll ML, Rubin LG. Incidence of occult bacteremia among highly febrile young children in the

era of the pneumococcal conjugate vaccine: a study from a children’s hospital emergency

department and urgent care center. Arch Pediatr Adolesc Med 2004;158(7):671–5.

[115] Yang YJ, Huang MC, Wang SM, et al. Analysis of risk factors for bacteremia in children with

nontyphoidal Salmonella gastroenteritis. Eur J Clin Microbiol Infect Dis 2002;21(4):290–3.

[116] Zaidi E, Bachur R, Harper M. Non-typhi Salmonella bacteremia in children. Pediatr Infect

Dis J 1999;18(12):1073–7.

[117] Kuppermann N, Malley R, Inkelis SH, et al. Clinical and hematologic features do not reliably

identify children with unsuspected meningococcal disease. Pediatrics 1999;103(2):E20.

ishimine192

[118] Wang VJ, Kuppermann N, Malley R, et al. Meningococcal disease among children who live

in a large metropolitan area, 1981–1996. Clin Infect Dis 2001;32(7):1004–9.

[119] Wang VJ, Malley R, Fleisher GR, et al. Antibiotic treatment of children with unsuspected

meningococcal disease. Arch Pediatr Adolesc Med 2000;154(6):556–60.

[120] Mandl K, Stack A, Fleisher G. Incidence of bacteremia in infants and children with fever and

petechiae. J Pediatr 1997;131(3):398.

[121] Nielsen HE, Andersen EA, Andersen J, et al. Diagnostic assessment of haemorrhagic rash and

fever. Arch Dis Child 2001;85(2):160–5.

[122] Wells LC, Smith JC, Weston VC, Collier J, et al. The child with a non-blanching rash: how

likely is meningococcal disease? Arch Dis Child 2001;85(3):218–22.

[123] American Academy of Pediatrics. Committee on Infectious Diseases. Prevention and control of

meningococcal disease. recommendations for use of meningococcal vaccines in pediatric

patients. Pediatrics 2005;116(2):496–505.

[124] Bachur R, Harper MB. Reevaluation of outpatients with Streptococcus pneumoniae bacteremia.

Pediatrics 2000;105(3 Pt 1):502–9.

[125] Bandyopadhyay S, Bergholte J, Blackwell CD, et al. Risk of serious bacterial infection in

children with fever without a source in the post-Haemophilus influenzae era when antibiotics

are reserved for culture-proven bacteremia. Arch Pediatr Adolesc Med 2002;156(5):512–7.

[126] Norberg A, Christopher NC, Ramundo ML, et al. Contamination rates of blood cultures

obtained by dedicated phlebotomy vs intravenous catheter. JAMA 2003;289(6):726–9.

[127] Waltzman ML, Harper M. Financial and clinical impact of false-positive blood culture results.

Clin Infect Dis 2001;33(3):296–9.

[128] Thuler LC, Jenicek M, Turgeon JP, et al. Impact of a false positive blood culture result on the

management of febrile children. Pediatr Infect Dis J 1997;16(9):846–51.

[129] DeAngelis C, Joffe A, Wilson M, et al. Iatrogenic risks and financial costs of hospitalizing

febrile infants. Am J Dis Child 1983;137(12):1146–9.

[130] Evidence based clinical practice guideline for outpatient management of fever of uncertain

source in children 2 to 36 months of age. 2003. Available at http://www.cincinnatichildrens.org/

svc/alpha/h/health-policy/ev-based/feverii.htm. Accessed August 1, 2005.

[131] Kuppermann N. The evaluation of young febrile children for occult bacteremia: time to

reevaluate our approach? Arch Pediatr Adolesc Med 2002;156(9):855–7.

[132] Baraff LJ, Bass JW, Fleisher GR, et al for the Agency for Health Care Policy and Research.

Practice guideline for the management of infants and children 0 to 36 months of age with fever

without source. Ann Emerg Med 1993;22(7):1198–210.

[133] Baraff LJ. Clinical policy for children younger than three years presenting to the emergency

department with fever [editorial]. Ann Emerg Med 2003;42(4):546–9.

[134] Green S, Rothrock S. Evaluation styles for well-appearing febrile children: are you a ‘‘risk-

minimizer’’ or a ‘‘test-minimizer’’? Ann Emerg Med 1999;33(2):211–4.

[135] Hoberman A, Chao HP, Keller DM, et al. Prevalence of urinary tract infection in febrile infants.

J Pediatr 1993;123(1):17–23.

[136] Shaw KN, Gorelick M, McGowan KL, et al. Prevalence of urinary tract infection in febrile

young children in the emergency department. Pediatrics 1998;102(2):E16.

[137] Bachur R, Harper MB. Reliability of the urinalysis for predicting urinary tract infections in

young febrile children. Arch Pediatr Adolesc Med 2001;155(1):60–5.

[138] Gorelick MH, Shaw KN. Clinical decision rule to identify febrile young girls at risk for urinary

tract infection. Arch Pediatr Adolesc Med 2000;154(4):386–90.

[139] Gorelick MH, Hoberman A, Kearney D, et al. Validation of a decision rule identifying

febrile young girls at high risk for urinary tract infection. Pediatr Emerg Care 2003;19(3):

162–4.

[140] Schoen EJ, Colby CJ, Ray GT. Newborn circumcision decreases incidence and costs of urinary

tract infections during the first year of life. Pediatrics 2000;105(4 Pt 1):789–93.

[141] Task Force on Circumcision. Circumcision policy statement. Pediatrics 1999;103(3):686–93.

[142] Zorc JJ, Kiddoo DA, Shaw KN. Diagnosis and management of pediatric urinary tract infec-

tions. Clin Microbiol Rev 2005;18(2):417–22.

http://www.cincinnatichildrens.org/svc/alpha/h/health-policy/ev-based/feverii.htm


[143] Huicho L, Campos-Sanchez M, Alamo C. Metaanalysis of urine screening tests for determin-

ing the risk of urinary tract infection in children. Pediatr Infect Dis J 2002;21(1):1–11.

[144] Wubbel L, Muniz L, Ahmed A, et al. Etiology and treatment of community-acquired

pneumonia in ambulatory children. Pediatr Infect Dis J 1999;18(2):98–104.

[145] Margolis P, Gadomski A. Does this infant have pneumonia? JAMA 1998;279(4):308–13.

[146] Jadavji T, Law B, Lebel MH, et al. A practical guide for the diagnosis and treatment of pediatric

pneumonia. CMAJ 1997;156(5):703.

[147] Lynch T, Platt R, Gouin S, et al. Can we predict which children with clinically suspected

pneumonia will have the presence of focal infiltrates on chest radiographs? Pediatrics 2004;

113(3 Pt 1):E186–9.

[148] Rothrock SG, Green SM, Fanelli JM, et al. Do published guidelines predict pneumonia in

children presenting to an urban ED? Pediatr Emerg Care 2001;17(4):240–3.

[149] Leventhal JM. Clinical predictors of pneumonia as a guide to ordering chest roentgenograms.

Clin Pediatr (Phila) 1982;21(12):730–4.

[150] Taylor JA, Del Beccaro M, Done S, et al. Establishing clinically relevant standards for tachy-

pnea in febrile children younger than 2 years. Arch Pediatr Adolesc Med 1995;149(3):

283–7.

[151] Zukin DD, Hoffman JR, Cleveland RH, et al. Correlation of pulmonary signs and symptoms

with chest radiographs in the pediatric age group. Ann Emerg Med 1986;15(7):792–6.

[152] Mower WR, Sachs C, Nicklin EL, et al. Pulse oximetry as a fifth pediatric vital sign. Pediatrics

1997;99(5):681–6.

[153] Tanen DA, Trocinski DR. The use of pulse oximetry to exclude pneumonia in children. Am J

Emerg Med 2002;20(6):521–3.

[154] Davies HD, Wang EE, Manson D, et al. Reliability of the chest radiograph in the diagnosis

of lower respiratory infections in young children. Pediatr Infect Dis J 1996;15(7):600–4.

[155] McCarthy PL, Spiesel SZ, Stashwick CA, et al. Radiographic findings and etiologic diagnosis

in ambulatory childhood pneumonias. Clin Pediatr (Phila) 1981;20(11):686–91.

[156] Courtoy I, Lande AE, Turner RB. Accuracy of radiographic differentiation of bacterial from

nonbacterial pneumonia. Clin Pediatr (Phila) 1989;28(6):261–4.

[157] Swingler GH, Hussey GD, Zwarenstein M. Randomised controlled trial of clinical outcome

after chest radiograph in ambulatory acute lower-respiratory infection in children. Lancet 1998;

351(9100):404–8.

[158] Bachur R, Perry H, Harper MB. Occult pneumonias: empiric chest radiographs in febrile

children with leukocytosis. Ann Emerg Med 1999;33(2):166–73.

[159] British Thoracic Society of Standards of Care Committee. BTS Guidelines for the manage-

ment of community acquired pneumonia in childhood. Thorax 2002;57:1–24.

[160] Black SB, Shinefield HR, Ling S, et al. Effectiveness of heptavalent pneumococcal conjugate

vaccine in children younger than five years of age for prevention of pneumonia. Pediatr Infect

Dis J 2002;21(9):810–5.

[161] Lee KC, Finkelstein JA, Miroshnik IL, et al. Pediatricians’ self-reported clinical practices and

adherence to national immunization guidelines after the introduction of pneumococcal

conjugate vaccine. Arch Pediatr Adolesc Med 2004;158(7):695–701.

[162] Klein JO. Management of the febrile child without a focus of infection in the era of universal

pneumococcal immunization. Pediatr Infect Dis J 2002;21(6):584–8 [discussion: 613–4].

[163] O’Brien KL, Santosham M. Potential impact of conjugate pneumococcal vaccines on pediatric

pneumococcal diseases. Am J Epidemiol 2004;159(7):634–44.

[164] Fernandez Lopez A, Luaces Cubells C, Garcia Garcia JJ, et al. Procalcitonin in pediatric

emergency departments for the early diagnosis of invasive bacterial infections in febrile infants:

results of a multicenter study and utility of a rapid qualitative test for this marker. Pediatr Infect

Dis J 2003;22(10):895–903.

[165] Galetto-Lacour A, Zamora SA, Gervaix A. Bedside procalcitonin and C-reactive protein tests in

children with fever without localizing signs of infection seen in a referral center. Pediatrics

2003;112(5):1054–60.

[166] Gendrel D, Raymond J, Coste J, et al. Comparison of procalcitonin with C-reactive protein,

ishimine194

interleukin 6 and interferon-alpha for differentiation of bacterial vs. viral infections. Pediatr

Infect Dis J 1999;18(10):875–81.

[167] Hsiao AL, Baker MD. Fever in the new millennium: a review of recent studies of markers

of serious bacterial infection in febrile children. Curr Opin Pediatr 2005;17(1):56–61.

[168] Isaacman DJ, Burke BL. Utility of the serum C-reactive protein for detection of occult bacterial

infection in children. Arch Pediatr Adolesc Med 2002;156(9):905–9.

[169] Pulliam PN, Attia MW, Cronan KM. C-reactive protein in febrile children 1 to 36 months of age

with clinically undetectable serious bacterial infection. Pediatrics 2001;108(6):1275–9.

[170] van Rossum AM, Wulkan RW, Oudesluys-Murphy AM. Procalcitonin as an early marker of

infection in neonates and children. Lancet Infect Dis 2004;4(10):620–30.

[171] Carrol ED, Newland P, Riordan FA, et al. Procalcitonin as a diagnostic marker of me-

ningococcal disease in children presenting with fever and a rash. Arch Dis Child 2002;86(4):

282–5.

fever without source in children 0 to 36 months of age · fever, one of the most common chief...

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